Control of GSK3beta nuclear localization by amino acid signaling requires GATOR1 but is mTORC1 independent

The availability of certain amino acids regulates cell survival, proliferation, growth, differentiation, and other cellular functions. Sensing of amino acids that converges on the GATOR1 and GATOR2 complexes supports activation of mTORC1 during amino acid replete conditions. Whether amino acid-derived cues regulate additional pathways remains poorly understood. We uncover that amino acid sensing involving GATOR1 and GATOR2 regulates the cellular localization of glycogen synthase kinase 3{beta} (GSK3{beta}). GATOR1 is required to recruit a subset of GSK3{beta} to the lysosome selectively in the presence of amino acids. In addition, while under nutrient replete conditions GSK3{beta} is largely cytosolic, amino acid starvation drives a portion of GSK3{beta} into the nucleus. Acute replenishment of specific amino acids in starved cells triggered nuclear exit of GSK3{beta}. This amino acid-stimulated GSK{beta} nuclear exit required GATOR1 and GATOR2 but was independent of mTORC1 and its activating RagA/B GTPases. This suggests that GATOR1 has a function that diverges from control of mTORC1 to regulate the nucleocytoplasmic shuttling of GSK3{beta}. Furthermore, experimental restriction of GSK3{beta} to the cytoplasm decreased cell survival in amino acid deficient conditions. This suggests that control of GSK3{beta} nuclear localization by GATOR-dependent signals represents a cellular adaptation to metabolic stress that supports cell survival.